The various known antihypertensive medications (i.e., drugs which lower blood pressure) can be generally classed by their in vivo modes of action.
One class of drugs called, collectively, the veratrum alkaloids, is effective in lowering blood pressure because the compounds are able to "fool" the brain into thinking that blood pressure is high. The brain then reflexly lowers blood pressure. Although effective for lowering blood pressure, the veratrum alkaloids have adverse side effects and hence their use as antihypertensive medication has become obsolete.
The presently used drugs for antihypertension generally either act within the brain to inhibit neurons or to interfere with peripheral nerve endings and the adjacent blood vessels. An example of the former are clonidine-type drugs. An example of the latter is guanethidine.
Dynorphin is a porcine pituitary peptide which contains seventeen amino acids and has potent agonist properties in guinea pig ileum and mouse vas deferens. Both dynorphin(1-13) and dynorphin(1-17) have been sequenced and synthesized. The synthetic dynorphin(1-13) product has been found to be as potent in bioassays as the naturally occuring peptide, but has been shown to be relatively weak in producing analgesia in studies with mice.
It has been reported that dynorphin(1-13), but not the shorter fragment dynorphin(1-9), has significant effects on opiate and beta-endorphin-induced analgesia in naive animals. The studies have suggested that dynorphin(1-13) may interact with other analgesic opioids. Thus, it has been shown that dynorphin(1-13) appears to interact with morphine to significantly modify the analgesia produced by morphine in naive animals. Therapeutic uses of dynorphin, particularly dynorphin(1-13), for hosts tolerant to narcotic analgesics are described in U.S. Pat. No. 4,361,553, inventors Horace H. Loh and Nancy M. Lee, issued Nov. 30, 1982. Use of dynorphin(1-10) amide to potentiate narcotic induced analgesia in tolerant hosts is described in pending U.S. patent application Ser. No. 387,005, filed June 10, 1982, entitled "Dynorphin Amide Analogs", inventors Lee, et al.
The first thirteen amino acids of dynorphin, or dynorphin(1-13), have the sequence: ##STR1## The N-terminal end contains Leu-enkephalin (those amino acids numbered 1-5), followed by the C-terminal extension (those amino acids numbered 6-13). Dynorphin's structure is quite different from known antihypertensive drugs such as the veratrum alkaloids, clonidine and sympatholytic type drugs.